Last week, the Wall Street Journal published an informative article on the emergence of cancer immunotherapies designed to augment the immune system's ability to recognize and combat malignant tumors. The oncology community is embracing this new treatment paradigm based on mounting clinical evidence that immunotherapies can produce long-term responses across multiple tumor types when combined with traditional therapies. As per the article, industry analysts project that immunotherapies could represent half of all cancer treatments within the next 10 years. The opportunity in lung cancer alone was referenced as a $6 billion opportunity.

At least five major drug companies are advancing candidates, including Bristol-Myers Squibb, whose drug Yervoy is already approved for melanoma. Drug mechanisms that inhibit the PD-1 molecular pathway, which cancer cells hijack to evade destruction by the body's immune system, are a primary target in the emerging immunotherapy pipeline. The article also balanced the compelling promise of these candidates with the reality that PD-1 inhibitors and other immunotherapies face significant administration and cost hurdles. Much of the concern is associated with the challenge of stacking an immunotherapeutic drug on top of the toxicity of established therapies such as radiation, chemotherapy, targeted cancer agents or other PD-1 inhibitors. Beyond this challenge, the cost of combining such therapies could prove to be prohibitive considering that Yervoy alone costs $120,000 for four doses administered over 12 weeks.

From an Aethlon Medical perspective, the Wall Street Journal article serves to reinforce our vision that a medical device can deliver immunotherapeutic benefit to both established and candidate cancer therapies, and do so economically and without added drug toxicity.

Our device strategy targets a survival mechanism deployed by tumors to evade and defeat the immune system of cancer patients. This mechanism, which is not addressed by drug therapies, is the seretion of exosomes by cancerous tumors. Researchers have discovered that tumors release these particles to trigger the death of cancer fighting immune cells and facilitate the spread of metastasis. Additionally, the systemic elimination of exosomes may represent a novel strategy to inhibit the PD-1 molecular pathway. To date, researchers have demonstrated that the Aethlon Hemopurifier® can capture exosomes underlying lymphoma, melanoma, ovarian, and breast cancer. If you are not familiar with the Hemopurifier®, it is a first-in-class medical device that targets the rapid elimination of life-threatening infectious viruses and tumor-secreted exosomes from circulation.

Based on the recent approval (after 5+ years of effort) of an investigational device exemption (IDE) by FDA, we are preparing to initiate the first U.S. studies of Hemopurifier® therapy in Hepatitis-C (HCV) infected individuals. In studies previously conducted overseas, Hemopurifier® therapy was demonstrated to accelerate viral load depletion in hardest-to-treat HCV patients receiving standard-of-care drug therapy.

As a result of crossing the IDE approval threshold, we opened the door to advance relationships with medical institutes that have clinical interest in expanding Hemopurifier® indications to include various forms of cancer.

When we initiated our first cancer research activities, we were making two intuitive yet forward-looking bets. The first was that exosomes would emerge to become a vital therapeutic target. The second was a belief that novel immunotherapies would rethink the landscape for treating cancer. Today, tumor-secreted exosomes are well-documented therapeutic targets and cancer immunotherapies are expected to take center stage in the cancer treatment arena. There is growing hope that the marriage of traditional cancer therapies with next-generation immunotherapies may someday allow cancer to become a manageable condition much like HIV-infection is managed through a cocktail of treatment mechanisms. At Aethlon Medical, our role is to provide the oncology community with a therapeutic tool that counters the immunosuppressive impact of exosomes without adding drug toxicity to companion cancer therapies.

In closing, I am providing the scientific viewpoint of Dr. Douglas Taylor on the potential implications of Hemopurifier® therapy in cancer care. Dr. Taylor is credited with the discovery of tumor-secreted exosomes and is a leading published author on the topic. He is also one of the newest members of the Aethlon family as he has accepted the position of Chief Scientific Officer at our Exosome Sciences diagnostic subsidiary. The following is a statement from Dr. Taylor:

Evidence indicates that molecules, such as programmed cell death-1 (PD-1) and CTLA-4, are exploited by tumors to suppress patient immune surveillance, allowing the progression of cancers. These molecules and their ligands negatively regulate anti-tumor immune responses, particularly CD8+ effector T cells. Treatment of activated T cells with anti-PD-L1 antibodies reduce T cell proliferation, which correlates with attenuated IL-2 secretion. In vitro cytotoxicity studies and in vivo growth inhibition can be restored utilizing anti-PD-L1 antibodies or by genetic silencing of PD-1. The expression of PD-L1 on tumor cells inhibits anti-tumor immunity through engagement of PD-1 on effector T cells. Expression of PD-L1 on tumors is correlated with reduced survival in many tumor types.

Due to the role of these molecules in immune regulation and correlation with cancer outcomes, these pathways are being targeted for immunotherapy. Bristol Myers' experimental PD-1 inhibitor Nivolumab and Merck's candidate, MK-3475, block the PD-1/PD-L1 interaction, allowing the immune system to react with the tumor cells. Yervoy targets a similar checkpoint, inhibiting the CTLA-4 pathway. Unlike genetically targeted drugs, which disrupt mutations that fuel tumor growth, the new agents treat the immune system. Current interest in targeting these molecular pathways raises a concern that their normal function acts as to modulate the immune system to prevent attacks on healthy cells. Studies in murine models deficient for PD-1 developed dilated cardiomyopathy and congestive heart failure and that expression of PD-1 may also prevent autoimmune diseases. Based on the critical role of PD-1 and CTLA-4, targeting their expression may be problematic resulting in serious side effects on the host. However, an essential component of the activity of such molecules may be due to their presence on exosomes released by tumor cells. We previously demonstrated the presence of these immunoregulatory molecules on tumor-derived exosomes and their ability to suppress T cell activation and proliferation (Taylor et al. Clinical Cancer Research, 9: 5113-5119, 2003). Thus, a reasonable approach that does not result in systemic toxicity would be the removal of these immunoregulatory molecules. Consequently, the ability of the Hemopurifier® to remove these circulating exosomes may provide a superior approach to treat these patients without the generalized inhibition of the respective molecular pathways.

About Aethlon Medical, Inc.

Aethlon Medical creates innovative medical devices to address life-threatening diseases. The Aethlon ADAPT™ (Adaptive Dialysis-like Affinity Platform Technology) establishes the basis for a new class of therapeutics that target the rapid elimination of disease enabling particles from the circulatory system of treated patients. The lead Aethlon ADAPT™ product is the Hemopurifier®, a device that addresses a broad-spectrum of viral pathogens as well as tumor-secreted exosomes that suppress the immune system of cancer patients. Aethlon is also operating under two government contracts with the Defense Advanced Research Projects Agency (DARPA) related the development of a medical device to reduce the incidence of sepsis. Exosome Sciences, Inc. is a majority owned Aethlon subsidiary that is advancing exosome-based strategies to diagnose and monitor cancer and infectious disease progression. Additional information can be found at www.AethlonMedical.com

Certain statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, that the FDA will not approve the initiation of the Company's clinical programs or provide market clearance of the company's products, future human studies whether revenue or non-revenue generating of the Aethlon ADAPT™ system or the Aethlon Hemopurifier® as an adjunct therapy to improve patient responsiveness to established cancer or hepatitis C therapies or as a standalone cancer or hepatitis C therapy, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the Company's ability to manufacture its products either internally or through outside companies and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, the ability of the Company to meet the milestones contemplated in the DARPA contract, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.